Abstract: The present invention relates to an agonist of the colony stimulating factor 1 receptor (CSF1R) for use in the prophylaxis and/or treatment of viral infections in states of immunosuppression in a subject and to pharmaceutical compositions comprising said CSF1R agonist. According to the invention, said subject is in a state of immunosuppression, when in said subject the absolute number of CD14+, CD16+ und HLA-DR+ expressing monocytes is reduced when compared to a healthy control subject. The invention is based on the finding that CSF1R agonist treatment, such as M-CSF treatment, induces an integrated multistep differentiation cascade that culminated in increased NK cell activation protecting HCT recipients from a viral infection. A mechanism of action by which M-CSF-induced myelopoiesis can rapidly reconstitute antiviral activity under immunosuppressed conditions was identified, which provides a general paradigm to boost innate antiviral immune response.

Abstract: The invention provides human phagocytic cells which are not tumorigenic, yet still capable of cell division ex-vivo, such as in cell culture. A culture containing these cells can be expanded manyfold, that is the cell number in such a culture can be increased by a factor of 10 or more. The cells show characteristics of functional phagocytes in a differentiated state and are capable to alleviate pathological defects in in vivo models.

Abstract: The present invention to the use of human term placenta as a source of HLA-matched cells for use in cell therapy, in particular wherein the cells are non-maternal macrophages. The invention also relates to two different sets of isolated placental macrophages of embryonic origin, which have been newly discovered and identified as being useful for macrophage cell therapy, and to methods to isolate these cells from human term placenta.

Abstract: The present invention relates to a human macrophage for use in cancer therapy, said human macrophage comprising at least one mutation in both alleles of a chromosomal gene, wherein said macrophage is resistant to tumor-induced reprogramming and/or shows anti-tumor activity. The human macrophage of the invention demonstrates typical markers of an M1 macrophage, such as the presence of MHC class II proteins, even after having been cultured in an environment which promotes M2-polarization, such as in the presence of M-CSF and/or IL4 and/or IL13. The invention also relates to a collection of human macrophages of the invention, to their use in medicine, and in particular to their use in cancer therapy such as the treatment of solid tumors as a preferred example.

Abstract: The present invention relates to methods for expanding a population of alveolar macrophages in a long term culture. In particular, an object of the present invention relates to a method of expanding a population of alveolar macrophages in a long term culture comprising culturing the population of alveolar macrophages in a culture medium supplemented with an amount of GM-CSF.

Abstract: The invention relates to methods and compositions comprising a macrophage colony stimulating factor (M-CSF) polypeptide or an agonist of the M-CSF receptor for preventing or treating myeloid cytopenia and related complications (such as infections) in a patient in need thereof (such as a patient undergoing hematopoietic stem cell transplantation).

Abstract: The present invention relates to methods for expanding a population of alveolar macrophages in a long term culture. In particular, an object of the present invention relates to a method of expanding a population of alveolar macrophages in a long term culture comprising culturing the population of alveolar macrophages in a culture medium supplemented with an amount of GM-CSF.

Abstract: The present invention relates to MafB mutants and uses thereof for research, screening and therapeutic purposes. In particular, the present invention relates to a MafB mutant polypeptide comprising the sequence as set forth in SEQ ID NO: 1 or 2 or a function conservative variant thereof wherein the glutaminic acid residue at position 269 has been deleted or substituted with a basic amino acid. The present invention also relates to a MafB mutant polypeptide comprising the sequence as set forth in SEQ ID NO: 1 or 2 or a function conservative variant thereof wherein the valine residue at position 277 has been deleted or substituted with a polar amino acid.

Abstract: The invention relates to methods and compositions comprising a macrophage colony stimulating factor (M-CSF) polypeptide or an agonist of the M-CSF receptor for preventing or treating myeloid cytopenia and related complications (such as infections) in a patient in need thereof (such as a patient undergoing hematopoietic stem cell transplantation).

Abstract: Mouse or human hematopoietic cells are transduced in vitro with one or more vectors encoding c-Myc and Klf4 genes, to overexpress both c-Myc and Klf4. The transduced cells produce self-renewing populations of macrophages, monocytes, monocyte-derived macrophages, B lymphocytes or erythroid cells. The self-renewing cell populations may include a pharmaceutical composition.

Abstract: The invention relates to an ex vivo method for expanding monocytes, macrophages or dendritic cells, which method comprises inhibiting the expression or the activity of MafB and c-Maf in monocytes, macrophages or dendritic cells; and expanding the cells in the presence of at least one cytokine or an agonist of cytokine receptor signalling.

Abstract: The invention relates to an ex vivo method for expanding monocytes, macrophages or dendritic cells, which method comprises inhibiting the expression or the activity of MafB and c-Maf in monocytes, macrophages or dendritic cells; and expanding the cells in the presence of at least one cytokine or an agonist of cytokine receptor signalling.

Abstract: The invention relates to an ex vivo method for expanding monocytes, macrophages or dendritic cells, which method comprises inhibiting the expression or the activity of MafB and c-Maf in monocytes, macrophages or dendritic cells; and expanding the cells in the presence of at least one cytokine or an agonist of cytokine receptor signaling.

Abstract: The invention relates to an ex vivo method for expanding monocytes, macrophages or dendritic cells, which method comprises inhibiting the expression or the activity of MafB and c-Maf in monocytes, macrophages or dendritic cells; and expanding the cells in the presence of at least one cytokine or an agonist of cytokine receptor signaling.

Abstract: The present invention relates to a method for inducing proliferation of functionally differentiated somatic cells comprising a step of activating expression of a Myc family gene and a KIf family gene in said cells or contacting said cells with a Myc family protein and a KIf family protein.

Abstract: The invention relates to an ex vivo method for expanding monocytes, macrophages or dendritic cells, which method comprises inhibiting the expression or the activity of MafB and c-Maf in monocytes, macrophages or dendritic cells; and expanding the cells in the presence of at least one cytokine or an agonist of cytokine receptor signaling.

Abstract: The invention relates to an ex vivo method for expanding monocytes, macrophages or dendritic cells, which method comprises inhibiting the expression or the activity of MafB and c-Maf in monocytes, macrophages or dendritic cells; and expanding the cells in the presence of at least one cytokine or an agonist of cytokine receptor signaling.

Abstract: The present invention finds the optimum organization of compiled code within an application to ensure maximal cache efficiency. A configuration file specifies predefined cache, optimization, and application parameters. The cache parameters include a cache size, cache line size, set associativity, address-to-cache-line mapping algorithm, and set replacement algorithm. The optimization parameters specify the minimum acceptable efficiency level. The application parameters include a list of object modules and functions within those modules. All possible orderings of the modules are stepped through to determine where the specified functions fall within the cache given the location of the function within the module. The function locations in each permutation of the orderings are analyzed to find a solution that matches or beats the optimization parameters. In an embodiment, a front-end analysis program (“tool”) and a back-end processing stage, usually related to a linker, are provided.